C1 inhibitor prevents adverse events from immunoglobulin replacement therapy

Key takeaways:

• Immunoglobulin replacement therapy triggered severe neuropathy.
• A 4,200 U dose of rhc1-INH enabled therapy without any adverse events.
• There were no ED visits or hospitalizations either.

ANAHEIM, Calif. — A woman who could not tolerate immunoglobulin replacement therapy benefitted from C1-INH replacement therapy, according to a presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

The patient, aged 65 years, had common variable immunodeficiency (CVID) with trough IgG of approximately 200 mg/dL and a target subcutaneous immunoglobulin dose (SCIG) of 20 g once a week.

However, this patient was unable to tolerate even 1 gram of IV immunoglobulin (IVIG) due to adverse events, Douglas H. Jones, MD, FAAAAI, FACAAI, director of Rocky Mountain Allergy at Tanner Clinic, told Healio.

“She was getting frequent and severe side effects to IVIG. She could not tolerate it,” Jones, who also is a member of the Healio Allergy/Asthma Peer Perspective Board, told Healio. “She was getting significant peripheral neuropathy, very debilitating side effects.”

Jones classified the neuropathy as severe, with burning and pins-and-needles sensations in her extremities and twitching for several days after treatment.

Consequently, this patient also could not have IVIG administered and her IgG trough levels were so low she experienced life-threatening infections and multiple hospitalizations, including one that resulted in admission to the ICU for pneumonia.

“She was in full-blown sepsis, was there for almost a week, close to dying, all because she just had little to no antibody levels,” Jones said.

Multiple reductions that eventually resulted in a 0.5 g dose did not improve these side effects.

Jones and his colleagues reviewed the literature and found a proposal that a C1 inhibitor such as C1 esterase inhibitor (recombinant), also known as rhC1-INH, (Ruconest, Pharming Healthcare) administered before the IVIG infusion could help with the peripheral neuropathy.

“Typically, the on-label use for it would be for acute hereditary angioedema attacks in adolescents and adults,” Jones said.

As an IV medication, rhC1-INH is administered with a small butterfly needle. Most patients learn how to administer it to themselves in just 5 minutes, Jones said,

“I had to petition insurance to get an off-label approval in this case,” Jones said.

The insurance company denied the petition at first but approved treatment after the patient was admitted to the ICU and Jones petitioned the company again.

“It still wasn’t easy,” he said.

The patient received 4,200 U of rhC1-INH intravenously for approximately 5 minutes an hour before the administration of 1 g of subcutaneous immunoglobulin (SCIG) on day 1. Jones reported that the SCIG was well tolerated with minimal adverse events.

“We started with just small amounts to make sure she tolerated it,” Jones said.

On days 2 and 3, the patient received 3 g of SCIG, again with no adverse events.

The patient now tolerates the recommended dose of 20 g of SCIG once a week with at-home, routine pretreatment of 4,200 U of rhC1-INH an hour before SCIG administration.

The duration of the effect of rhC1-INH, which Jones characterized as 3 days or longer, was consistent with the profile that has been observed in patients with hereditary angioedema.

Insurance coverage issues have caused brief interruptions in this pretreatment regimen, but the patient has been following it successfully for approximately a year without any debilitating neuropathy or other adverse events.

“Just a few minor infections that haven’t required any antibiotics,” Jones said.

The patient has not had any ED visits or hospitalizations over the past year either.

“What we wanted to do is get this in the literature because if there are other patients out there with perhaps severe CVID or other immune deficiency who are having side effects, such as peripheral neuropathy to the IVIG, Ruconest or another C1 inhibitor might be a nice option to alleviate side effects but also allow us to be able to get them their immunoglobulin replacement therapy,” Jones said.

Also, Jones said, this off-label case may help physicians better understand the mechanisms behind these reactions and support additional utilization in the future.

“It’s hypothesized that there’s an activation and a consumption of the complement proteins,” Jones said. “That’s something we need to see more.”

But based on these findings, Jones said, patients with adverse events related to their immunoglobulin replacement therapy may benefit from C1-INH replacement therapy including rhC1-INH before SCIG or IVIG for their primary immunodeficiency.

“She was in a severe life-threatening situation, and we were able to get her out of that with proper use of these medications,” Jones said.